19-Sep-2014 - Charité - Universitätsmedizin Berlin

New diagnostic method identifies genetic diseases

PhenIX can identify genetic diseases quickly and reliably based on analyses of genes and symptoms

People with genetic diseases often have to embark on an odyssey from one doctor to the next. Fewer than half of all patients who are suspected of having a genetic disease actually receive a satisfactory diagnosis. Scientists from the Charité - Universitätsmedizin Berlin and the Max Planck Institute for Molecular Genetics have now developed a test procedure that significantly increases the prospect of a diagnosis for affected patients. The procedure is freely available to the relevant medical institutions and can be used with immediate effect.

The first step to the right treatment is an accurate diagnosis - even in untreatable cases, it is invaluable. "At the least, it provides the reassurance that the illness is not self-inflicted," says Peter Robinson, one of the developers of the PhenIX diagnostic procedure. PhenIX stands for "Phenotypic Interpretation of eXomes". In the past, only a genetic analysis was carried out for such diseases. However, this is often not enough to accurately detect the illness. The problem with all the tests is that the individual diversity of patients makes a diagnostic analysis difficult – among the millions of genetic deviations from the norm inherent in every single person, the crucial difference must be found.

To solve this problem, the Berlin-based scientists developed an innovative diagnostic procedure. In contrast to previous diagnostic tests, PhenIX combines the analysis of genetic irregularities with the patient's clinical presentation. In the first step, a specific search is conducted for around 3,000 genes that are known to cause diseases. To find out which ones they are, the scientists systematically search through publicly available databases and create a list of known genetic defects. Once this is complete, several hundred genetic irregularities usually still remain in the patient's genome as candidates for the cause of the disease.

In the second step, the attending doctor browses the Human Phenotype Ontology (HPO), a database already developed at the Charité, to search for the patient's symptoms. This also contains a list of genetic defects that could be responsible for the disease. When the doctor then examines the overlap between the two analysis methods, he or she is left with a list of candidates of often no more than 20 possible causes of the illness, including a ranking in order of probability. It is relatively easy to go through this list and test it.

In a pilot study, a group of patients, whose genetic disease was already known, were examined. In every single case, PhenIX diagnosed the illness correctly. Other sick persons also presented for treatment. These were individuals who had not been able to obtain a diagnosis, despite intensive and in some cases years of effort and investigation. More than 25 percent of these patients were able to find out the exact cause of their illness when the PhenIX method was used. 

PhenIX is already available to hospitals that have the necessary technical equipment. "Through a combination of clinical findings and genetic analysis, we have taken a major step forward – the new method means just two hours of work for the doctor," says Robinson. And he promises: "Even in the future, a free version of this programme will always be available." He sees the potential for further improvement in a more standardised handling of the databases. "Doctors sometimes do not know exactly how they should describe a symptom, or they know a particular symptom under a different name." Certain guidelines could make the search process more successful, so that the diagnosis can be even faster and more accurate in the future.

  • Tomasz Zemojtel et al.; Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome; Science Translational Medicine, 3. September 2014

Charité - Universitätsmedizin Berlin

Request information now

Recommend news PDF version / Print

Share on

Facts, background information, dossiers
  • genetic diseases
  • diagnostics
  • databases
More about Charité
  • News

    Could the blood of COVID-19 patients be used to predict disease progression?

    Researchers from Charité – Universitätsmedizin Berlin and the Francis Crick Institute have identified 27 proteins which are present at different levels in the blood of COVID-19 patients, depending on the severity of their symptoms. These biomarker profiles could be used to predict disease p ... more

    Diagnostics, meet CRISPR

    A new diagnostic test to quickly and easily monitor kidney transplant patients for infection and rejection relies on a simple urine sample and a powerful partner: the gene-editing technology CRISPR. Michael Kaminski, who developed it, leads a new Emmy Noether Group at the MDC & Charité. The ... more

    Recognise and control new variants of the deadly Ebola virus more quickly

    The situation is extraordinary: there have only ever been four declarations of public health emergencies of international concern in the past and now there are two at the same time. Whilst the risks associated with the novel coronavirus are still unclear, people in the Democratic Republic o ... more

More about MPI für molekulare Genetik
  • News

    Breaks in the genome

    Breaks and rearrangements in the genome can lead to severe diseases, even if all genes remain intact. Hi-C, a method to map the three-dimensional structure of chromosomes, promises more reliable and accurate diagnoses of such defects, but is not used in the clinic yet. A team of researchers ... more

    Swiss Army Knife for Genome Research

    It is the the dream of every molecular geneticist: an easy-to-use program that compares data sets from different cellular conditions, identifies enhancer regions and then assigns them to their target genes. A research team led by Professor Martin Vingron at the Max Planck Institute for Mole ... more

    Decoding Lil BUB: Crowdfunded project reveals genome of internet celebrity cat

    Lil BUB has drawn millions of followers across the internet for her cute appearance. Behind the celebrity cat’s unique features is a combination of two rare genetic variants, three molecular biologists from Germany and the US report. The results of their crowdfunded project “LilBUBome” are ... more

More about Max-Planck-Gesellschaft
  • News

    Detecting the handedness of a single nanoparticle

    Scientists from the Micro, Nano and Molecular Systems Lab at the Max Planck Institute for Intelligent Systems have developed a new spectroscopic-microscope, which can be used to observe a single nanoparticle in real time. This enabled the first detection of a nanoparticle’s handedness while ... more

    Mass of the deuteron corrected

    High-precision measurements of the mass of the deuteron, the nucleus of heavy hydrogen, provide new insights into the reliability of fundamental quantities in atomic and nuclear physics. This is reported in the journal "Nature" by a collaboration led by the Max Planck Institute for Nuclear ... more

    Dissecting protein assemblies

    Super-resolution MINFLUX nanoscopy, developed by Nobel laureate Stefan Hell and his team, is able to discern fluorescent molecules that are only a few nanometers apart. In an initial application of this technique to cell biology, researchers led by Stefan Hell and Stefan Jakobs have now opt ... more